bcl-x Prevents Apoptotic Cell Death of Both Primitive and Definitive Erythrocytes at the End of Maturation

bcl-x is a member of the bcl-2 gene family, which regulates apoptotic cell death in various cell lineages. There is circumstantial evidence suggesting that bcl-x might play a role in the apoptosis of erythroid lineage cells, although there is no direct evidence. In this study, we used Bcl-X null mouse embryonic stem (ES) cells, and showed that Bcl-X is indispensable for the production of both embryonic primitive erythrocytes (EryP) and adult definitive erythrocytes (EryD) at the end of their maturation. In vivo, bcl-x−/− ES cells did not contribute to circulating EryD in adult chimeric mice that were produced by blastocyst microinjection of the bcl-x−/− ES cells. bcl-x−/− EryP and EryD were produced by in vitro differentiation induction of ES cells on macrophage colony-stimulating factor–deficient stromal cell line OP9, and further analysis was carried out. The emergence of immature EryP and EryD from bcl-x−/− ES cells was similar to that from bcl-x+/+ ES cells. However, prominent cell death of bcl-x−/− EryP and EryD occurred when the cells matured. The data show that the antiapoptotic function of bcl-x acts at the very end of erythroid maturation

Multidimensional imaging of liver injury repair in mice reveals fundamental role of the ductular reaction

Upon severe and/or chronic liver injury, ectopic emergence and expansion of atypical biliary epithelial-like cells in the liver parenchyma, known as the ductular reaction, is typically induced and implicated in organ regeneration. Although this phenomenon has long been postulated to represent activation of facultative liver stem/progenitor cells that give rise to new hepatocytes, recent lineage-tracing analyses have challenged this notion, thereby leaving the pro-regenerative role of the ductular reaction enigmatic. Here, we show that the expanded and remodelled intrahepatic biliary epithelia in the ductular reaction constituted functional and complementary bile-excreting conduit systems in injured parenchyma where hepatocyte bile canalicular networks were lost. The canalicular collapse was an incipient defect commonly associated with hepatocyte injury irrespective of cholestatic statuses, and could sufficiently provoke the ductular reaction when artificially induced. We propose a unifying model for the induction of the ductular reaction, where compensatory biliary epithelial tissue remodeling ensures bile-excreting network homeostasis

Relationship Between Impaired Microvascular Function in the Non-Infarct-Related Area and Left Ventricular Remodeling in Patients With Myocardial Infarction

Background. Myocardial flow reserve (MFR) in the non-infarct-related area (NIRA) has been reported to be impaired after the onset of myocardial infarction (MI). The aim of this study was to determine whether microvascular dysfunction in the NIRA is related to left-ventricular remodeling after MI. Methods. We prospectively studied 17 patients who suffered their first single-vessel MI, and who underwent successful revascularization. The MFR in the NIRA was assessed quantitatively using ^13N-ammonia positron emission tomography within 2 weeks after the onset. Peak creatinine kinase and the defect score on ^<99m>Tc-tetrofosmin myocardial perfusion imaging were used as an index of the severity of MI. The left-ventricular end-diastolic volume index (LVEDVI) was calculated using left ventriculography at 1 month and 6 months after the onset. Results. Patients with severely impaired MFR (< 2.09) had higher peak creatinine kinase values (6,000 ± 5,485 IU/L vs. 2,250 ± 1,950 IU/L, p = 0.0081), defect scores (16.3 ± 5.9 vs. 7.9 ± 6.5, p = 0.0404), and LVEDVI at 1 month (125.6 ± 34.4 mL/m^2 vs. 82.8 ± 17.7 mL/m^2, p = 0.0036) than those with mildly impaired MFR (≥ 2.09). Moreover, the differences of LVEDVI between the 2 groups persisted over 6 months (133.3 ± 43.6 mL/m^2 vs. 89.5 ± 17.3 mL/m^2, p = 0.0078). The MFR in the NIRA correlated inversely with the LVEDVI at 1 month and 6 months (r = -0.590, p = 0.0127 and r = -0.729, p = 0.0031, respectively). Conclusions. These data indicate that microvascular impairment in the NIRA might have contributed to left-ventricular remodeling after MI